Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2000-12-13
pubmed:databankReference
http://linkedlifedata.com/resource/pubmed/xref/GENBANK/AJ289841, http://linkedlifedata.com/resource/pubmed/xref/GENBANK/AJ289842, http://linkedlifedata.com/resource/pubmed/xref/GENBANK/AJ289843, http://linkedlifedata.com/resource/pubmed/xref/GENBANK/AJ289844, http://linkedlifedata.com/resource/pubmed/xref/GENBANK/AJ289845, http://linkedlifedata.com/resource/pubmed/xref/GENBANK/AJ289846, http://linkedlifedata.com/resource/pubmed/xref/GENBANK/AJ289847, http://linkedlifedata.com/resource/pubmed/xref/GENBANK/AJ289848, http://linkedlifedata.com/resource/pubmed/xref/GENBANK/AJ289849, http://linkedlifedata.com/resource/pubmed/xref/GENBANK/AJ289850, http://linkedlifedata.com/resource/pubmed/xref/GENBANK/AJ289851, http://linkedlifedata.com/resource/pubmed/xref/GENBANK/AJ289852, http://linkedlifedata.com/resource/pubmed/xref/GENBANK/AJ289853, http://linkedlifedata.com/resource/pubmed/xref/GENBANK/AJ289854, http://linkedlifedata.com/resource/pubmed/xref/GENBANK/AJ289855, http://linkedlifedata.com/resource/pubmed/xref/GENBANK/AJ289856, http://linkedlifedata.com/resource/pubmed/xref/GENBANK/AJ289857
pubmed:abstractText
Triple-A syndrome (MIM 231550; also known as Allgrove syndrome) is an autosomal recessive disorder characterized by adrenocorticotropin hormone (ACTH)-resistant adrenal insufficiency, achalasia of the oesophageal cardia and alacrima. Whereas several lines of evidence indicate that triple-A syndrome results from the abnormal development of the autonomic nervous system, late-onset progressive neurological symptoms (including cerebellar ataxia, peripheral neuropathy and mild dementia) suggest that the central nervous system may be involved in the disease as well. Using fine-mapping based on linkage disequilibrium in North African inbred families, we identified a short ancestral haplotype on chromosome 12q13 (<1 cM), sequenced a BAC contig encompassing the triple-A minimal region and identified a novel gene (AAAS) encoding a protein of 547 amino acids that is mutant in affected individuals. We found five homozygous truncating mutations in unrelated patients and ascribed the founder effect in North African families to a single splice-donor site mutation that occurred more than 2,400 years ago. The predicted product of AAAS, ALADIN (for alacrima-achalasia-adrenal insufficiency neurologic disorder), belongs to the WD-repeat family of regulatory proteins, indicating a new disease mechanism involved in triple-A syndrome. The expression of the gene in both neuroendocrine and cerebral structures points to a role in the normal development of the peripheral and central nervous systems.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1061-4036
pubmed:author
pubmed:issnType
Print
pubmed:volume
26
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
332-5
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:11062474-Abnormalities, Multiple, pubmed-meshheading:11062474-Adrenal Insufficiency, pubmed-meshheading:11062474-Africa, Northern, pubmed-meshheading:11062474-Amino Acid Motifs, pubmed-meshheading:11062474-Amino Acid Sequence, pubmed-meshheading:11062474-Chromosomes, Artificial, Bacterial, pubmed-meshheading:11062474-Chromosomes, Human, Pair 12, pubmed-meshheading:11062474-Codon, pubmed-meshheading:11062474-Consanguinity, pubmed-meshheading:11062474-DNA Mutational Analysis, pubmed-meshheading:11062474-Esophageal Achalasia, pubmed-meshheading:11062474-Evolution, Molecular, pubmed-meshheading:11062474-Expressed Sequence Tags, pubmed-meshheading:11062474-Genes, pubmed-meshheading:11062474-Haplotypes, pubmed-meshheading:11062474-Humans, pubmed-meshheading:11062474-Linkage Disequilibrium, pubmed-meshheading:11062474-Molecular Sequence Data, pubmed-meshheading:11062474-Nerve Tissue Proteins, pubmed-meshheading:11062474-Nervous System Diseases, pubmed-meshheading:11062474-Nuclear Pore Complex Proteins, pubmed-meshheading:11062474-Pedigree, pubmed-meshheading:11062474-Point Mutation, pubmed-meshheading:11062474-Proteins, pubmed-meshheading:11062474-Repetitive Sequences, Amino Acid, pubmed-meshheading:11062474-Sequence Alignment, pubmed-meshheading:11062474-Sequence Homology, Amino Acid, pubmed-meshheading:11062474-Species Specificity, pubmed-meshheading:11062474-Syndrome, pubmed-meshheading:11062474-Xerophthalmia
pubmed:year
2000
pubmed:articleTitle
Mutant WD-repeat protein in triple-A syndrome.
pubmed:affiliation
Unité de Recherches sur les Handicaps Génétiques de l'Enfant INSERM U-393, Paris, France.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't